Serum 25-hydroxyvitamin D levels and risk of all-cause and cause-specific mortality: A 14-year prospective cohort study.

ABSTRACT

BACKGROUND & AIMS: The circulating vitamin D level that is optimal for health is unknown. This study aimed to examine the association between circulating vitamin D level and risk of all-cause and cause-specific mortality. METHODS: This prospective cohort study included 18,797 Korean adults aged 40 years or older, living in rural areas, with no history of cancer or cardiovascular disease (CVD) at baseline. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at baseline. Participants were followed-up from the survey date (2005-2012) until December 31, 2021. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality by baseline vitamin D level. Restricted cubic splines were used to explore the nonlinearity. RESULTS: The median (interquartile range) of 25(OH)D level was 55.8 (40.8-71.8) nmol/L. During a median follow-up of 14.3 years, 2250 deaths were recorded. Compared with participants with a 25(OH)D level <30 nmol/L, higher vitamin D levels (30 to < 50, 50 to < 75, and ≥75 nmol/L) were associated with a lower risk of all-cause mortality HR (95% CI) of 0.82 (0.69-0.98), 0.74 (0.62-0.88), and 0.69 (0.57-0.84), respectively. A nonlinear relationship between vitamin D level and all-cause mortality was observed, with the risk plateauing between 50 and 60 nmol/L (p for nonlinearity = 0.009). The association was more pronounced for cancer-related mortality. HR 0.55 (95% CI 0.39-0.77) for a 25(OH)D level ≥75 nmol/L compared with <30.0 nmol/L. Low vitamin D levels were associated with increased CVD mortality in men. CONCLUSIONS: Vitamin D level was inversely associated with all-cause and cause-specific mortality in middle-aged and older adults. Maintaining a serum 25(OH)D level of approximately 50-60 nmol/L may contribute to longevity and warrants further investigation.